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New advances in nitroreductase detection and cell hypoxia imaging
 Date: 29-08-2013  Page Views:

Hypoxia, caused by an inadequate oxygen supply, is an important feature of many diseases including solid tumors. The hypoxic status of solid tumors has been considered to be an indicator of adverse prognosis because of tumor progression toward a more malignant phenotype with increased metastatic potential and resistance to treatment. Consequently, hypoxic cells usually provide a tumor-specific targeting strategy for therapy. Because of this, developing novel methods for hypoxia detection is of great importance. Prof. Ma Huimin, Dr. Li Xiaohua and his co-workers from CAS Key Laboratory of Analytical Chemistry for Living Biosystems have developed a highly selective and sensitive fluorescence probe, 7-[(5-nitrofuran-2-yl)methoxy]-3H-phenoxazin-3-one for imaging the hypoxic status of tumor cells via the indirect detection of nitroreductase (Figure 1, Anal. Chem. 2013, 85, 3926−3932). The detection mechanism is based on the fact that nitroreductase can selectively catalyze the reduction of the nitro group in 1 to a hydroxylamine or amino group in the presence of reduced nicotinamide adenine dinucleotide as an electron donor that is indispensable, followed by the 1,6-rearrangement−elimination and the release of resorufin. As a result, the reaction produces a distinct color and fluorescence change from almost colorless and nonfluorescent to pink and strong red fluorescence. The fluorescence increase of probe 1 at λ550/585 nm is directly proportional to the concentration of nitroreductase in the range of 15−300 ng/mL, with a detection limit of 0.27 ng/mL. The ready reduction of the nitro group in 1 under hypoxic conditions leads to the establishment of a sensitive and selective fluorescence method for imaging the hypoxic status of tumor cells, and with this method Hela and A549 cells under normoxic and hypoxic conditions (even for different extents of hypoxia) can be differentiated successfully. This method is simple and may be useful for the imaging of disease-relevant hypoxia.

Figure 1 Fluorescent probe for nitroreductase and its application in cell imaging

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